<SEC-DOCUMENT>0001654954-22-015089.txt : 20221114
<SEC-HEADER>0001654954-22-015089.hdr.sgml : 20221114
<ACCEPTANCE-DATETIME>20221114065853
ACCESSION NUMBER:		0001654954-22-015089
CONFORMED SUBMISSION TYPE:	6-K
PUBLIC DOCUMENT COUNT:		1
CONFORMED PERIOD OF REPORT:	20221114
FILED AS OF DATE:		20221114
DATE AS OF CHANGE:		20221114

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			ASTRAZENECA PLC
		CENTRAL INDEX KEY:			0000901832
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		IRS NUMBER:				000000000
		STATE OF INCORPORATION:			X0
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		6-K
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	001-11960
		FILM NUMBER:		221380015

	BUSINESS ADDRESS:	
		STREET 1:		1 FRANCIS CRICK AVENUE
		STREET 2:		CAMBRIDGE BIOMEDICAL CAMPUS
		CITY:			CAMBRIDGE
		STATE:			X0
		ZIP:			CB2 0AA
		BUSINESS PHONE:		011 44 20 7304 5000

	MAIL ADDRESS:	
		STREET 1:		1 FRANCIS CRICK AVENUE
		STREET 2:		CAMBRIDGE BIOMEDICAL CAMPUS
		CITY:			CAMBRIDGE
		STATE:			X0
		ZIP:			CB2 0AA

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	ZENECA GROUP PLC
		DATE OF NAME CHANGE:	19930422
</SEC-HEADER>
<DOCUMENT>
<TYPE>6-K
<SEQUENCE>1
<FILENAME>a2284g.htm
<DESCRIPTION>ENHERTU RECOMMENDED FOR EU APPROVAL IN GASTRIC
<TEXT>
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1.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
Enhertu recommended for EU approval in gastric</font></div>
</div>
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<font style="font-family: Times New Roman; font-size: 13px">14
November 2022 07:10 GMT</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
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<font style="font-family: Times New Roman; font-size: 13px"><font style="font-weight: bold; font-style: italic; font-size: 13px">
Enhertu</font>&#xA0;<font style="font-weight: bold; font-size: 13px">recommended for approval in
the EU by CHMP for patients with previously treated HER2-positive
advanced gastric cancer</font></font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
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<font style="color: #000000; font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
Based on DESTINY-Gastric02 which showed AstraZeneca and Daiichi
Sankyo's Enhertu demonstrated clinically meaningful efficacy and
DESTINY-Gastric01 which showed improved overall survival compared
to chemotherapy</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">AstraZeneca
and Daiichi Sankyo's&#xA0;<font style="font-style: italic">Enhertu</font>&#xA0;(trastuzumab deruxtecan)
has been recommended for approval in the European Union (EU) as
monotherapy for the treatment of adult patients with advanced
HER2-positive gastric or gastroesophageal junction (GEJ)
adenocarcinoma who have received a prior trastuzumab-based
regimen.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic">
Enhertu</font>&#xA0;is a specifically engineered HER2-directed
antibody drug conjugate (ADC) being jointly developed and
commercialised by AstraZeneca and Daiichi Sankyo.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency based its positive opinion on results
from the DESTINY-Gastric02 and the DESTINY-Gastric01 Phase II
trials.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
In DESTINY-Gastric02, conducted in patients from North America and
Europe, updated results showed treatment
with&#xA0;</font><font style="font-style: italic; color: #000000">Enhertu</font><font style="color: #000000">&#xA0;resulted in a confirmed objective response
rate (ORR) of 41.8% as assessed by independent central review
(ICR). Median duration of response (DoR) was 8.1 months and median
overall survival (OS) was 12.1 months. Primary r</font>esults from
the DESTINY-Gastric02 Phase II trial were presented at the 2021
European Society&#xA0;<font style="color: #000000">for Medical
Oncology (ESMO) Congress, with the updated data presented at ESMO
2022.</font><font style="font-size: 70%; vertical-align: top; color: #000000">1</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-size: 70%; vertical-align: top; color: #000000; font-family: Times New Roman">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
In DESTINY-Gastric01, conducted in patients from Japan and South
Korea, updated results showed treatment
with&#xA0;</font><font style="font-style: italic; color: #000000">Enhertu</font><font style="color: #000000">&#xA0;resulted in an ORR of 51.3% versus 14.3%
with chemotherapy (irinotecan or paclitaxel). Patients treated
with&#xA0;</font><font style="font-style: italic; color: #000000">Enhertu</font><font style="color: #000000">&#xA0;had a 40% reduction in the risk of death
versus patients treated with chemotherapy (based on a hazard ratio
of 0.60; 95% confidence interval: 0.42-0.86, p=0.01) with a median
OS of 12.5 months versus 8.9 months. Additionally, confirmed ORR, a
major efficacy outcome, was 42.0% with&#xA0;</font><font style="font-style: italic; color: #000000">Enhertu</font><font style="color: #000000">&#xA0;versus 12.5% with chemotherapy as assessed
by ICR. The primary analysis was published
in</font>&#xA0;<font style="font-style: italic; text-decoration: underline; color: #0000FF">The
New England Journal of Medicine</font><font style="font-style: italic">,</font><font style="font-size: 70%; vertical-align: top; color: #000000">2</font>&#xA0;with
the updated data presented at the 2021 American Society of Clinical
Oncology Annual Meeting.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; background-color: #FEFEFE; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Susan Galbraith, Executive Vice President, Oncology R&amp;D,
AstraZeneca, said:</font>&#xA0;<font style="color: #000000; background-color: #FEFEFE">"G</font><font style="color: #000000">astric cancer is usually diagnosed in the advanced
stage in many European countries and patients face high mortality
rates. If approved,</font>&#xA0;<font style="font-style: italic; color: #000000">Enhertu</font>&#xA0;<font style="color: #000000">would
be the first HER2-directed medicine for patients with advanced
gastric cancer in the European Union in more than a
decade."</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; background-color: #FEFEFE">
Ken Takeshita, Global Head,</font>&#xA0;<font style="background-color: #FEFEFE">Oncology R&amp;D, Daiichi
Sankyo</font>, Inc,&#xA0;<font style="background-color: #FEFEFE">sa</font><font style="color: #000000; background-color: #FEFEFE">id:</font>&#xA0;<font style="color: #000000; background-color: #FEFEFE">"</font><font style="font-style: italic; color: #000000; background-color: #FEFEFE">Enhertu</font><font style="color: #000000; background-color: #FEFEFE">&#xA0;is
the first HER2-directed medicine to demonstrate a significant
improvement in overall survival compared to chemotherapy in
patients with gastric cancer following initial treatment with a
HER2-directed medicine in the advanced or metastatic setting. The
CHMP opinion recognises the high unmet need in this patient
population and brings us one step closer to bringing this medicine
to patients with gastric cancer in Europe."</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
In both trials, the safety profiles observed in patients treated
with&#xA0;</font><font style="font-style: italic; color: #000000">Enhertu</font><font style="color: #000000">&#xA0;were consistent with those seen in other
trials of&#xA0;</font><font style="font-style: italic; color: #000000">Enhertu</font><font style="color: #000000">&#xA0;with no new safety signals
identified.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Enhertu</font>&#xA0;<font style="color: #000000">is approved in the
US and several other countries for locally advanced or metastatic
HER2-positive gastric cancer.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="text-decoration: underline; color: #000000; font-weight: bold; font-family: Times New Roman; font-size: 13px">
Notes</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
HER2-positive gastric cancer</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Gastric (stomach) cancer is the fifth most common cancer worldwide
and the fourth highest leading cause of cancer mortality, with a
five-year global survival rate of 5% to 10% for advanced or
metastatic disease.</font><font style="font-size: 70%; vertical-align: top; color: #000000">3-5</font><font style="color: #000000">&#xA0;Approximately
one million new patients were diagnosed with gastric cancer in
2020, with 768,000 deaths reported globally.</font><font style="font-size: 70%; vertical-align: top; color: #000000">6</font><font style="color: #000000">&#xA0;In
Europe, approximately 136,000 cases of gastric cancer are diagnosed
annually, and Eastern Europe has the second highest incidence of
gastric cancer worldwide after Eastern Asia.</font><font style="font-size: 70%; vertical-align: top; color: #000000">5-6</font><font style="color: #000000">&#xA0;Gastric
cancer is the sixth leading cause of cancer death in Europe and is
typically diagnosed in the advanced stage. Even when diagnosed in
earlier stages of the disease, the survival rate remains
modest.</font><font style="font-size: 70%; vertical-align: top; color: #000000">5-7</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Approximately one in five gastric cancers are
HER2-positive.</font><font style="font-size: 70%; vertical-align: top; color: #000000">8,9</font><font style="color: #000000">&#xA0;HER2
is a tyrosine kinase receptor growth promoting protein expressed on
the surface of many types of tumours including breast, gastric,
lung and colorectal cancers.</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</font><font style="color: #000000">&#xA0;HER2
overexpression may be associated with a specific HER2 gene
alteration known as HER2 amplification.</font><font style="font-size: 70%; vertical-align: top; color: #000000">9</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Recommended first-line treatment for HER2-positive advanced or
metastatic gastric cancer is combination chemotherapy plus
trastuzumab, an anti-HER2 medicine, which has been shown to improve
survival outcomes when added to chemotherapy.</font><font style="font-size: 70%; vertical-align: top; color: #000000">10</font><font style="color: #000000">&#xA0;For
patients with metastatic gastric cancer that progresses following
initial treatment with a trastuzumab-based regimen, treatment
options are limited, and in many regions in the world there are no
additional HER2 directed medicines available.</font><font style="font-size: 70%; vertical-align: top; color: #000000">2,11,12</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
DESTINY-Gastric02</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">DESTINY-Gastric02
is an open-label, single-arm Phase II trial in Western patients
evaluating the efficacy and safety of&#xA0;<font style="font-style: italic">Enhertu</font>&#xA0;(6.4mg/kg) in patients
with HER2-positive metastatic and/or unresectable gastric or GEJ
adenocarcinoma with disease progression on or after a
trastuzumab-containing regimen.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">The
primary endpoint of DESTINY-Gastric02 is confirmed ORR based on
ICR. Secondary endpoints include progression-free survival (PFS),
OS, DoR and safety.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">DESTINY-Gastric02
enrolled 79 patients at multiple sites in North America and
Europe.&#xA0;For more information about the trial,
visit&#xA0;<font style="text-decoration: underline; color: #0000FF">ClinicalTrials.gov</font><font style="font-style: italic">.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
DESTINY-Gastric01</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">DESTINY-Gastric01
is a randomised, open-label Phase II trial evaluating the efficacy
and safety of&#xA0;<font style="font-style: italic">Enhertu</font>&#xA0;(6.4mg/kg) in patients
from Japan and South Korea with primarily HER2-positive (defined as
immunohistochemistry [IHC] 3+ or IHC 2+/in-situ hybridisation
[ISH]+) advanced gastric cancer or GEJ adenocarcinoma whose tumours
have progressed on two or more prior treatment regimens including
fluoropyrimidine (5-FU), platinum chemotherapy and trastuzumab.
Patients were randomised 2:1 to receive&#xA0;<font style="font-style: italic">Enhertu</font>&#xA0;or physician's choice of
chemotherapy (paclitaxel or irinotecan monotherapy).</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">The
primary endpoint of DESTINY-Gastric01 is ORR. Secondary endpoints
include OS, PFS, DoR, disease control rate and time to treatment
failure, as well as pharmacokinetic and safety
endpoints.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">DESTINY-Gastric01
enrolled 187 patients at multiple sites in Japan and South Korea.
For more information about the trial, visit&#xA0;<font style="text-decoration: underline; color: #0000FF">ClinicalTrials.gov</font><font style="font-style: italic">.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
Enhertu</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic">
Enhertu&#xA0;</font>is a HER2-directed ADC. Designed using Daiichi
Sankyo's proprietary DXd ADC technology,&#xA0;<font style="font-style: italic">Enhertu&#xA0;</font>is the lead ADC in the
oncology portfolio of Daiichi Sankyo and the most advanced
programme in AstraZeneca's ADC scientific
platform.&#xA0;<font style="font-style: italic">Enhertu</font>&#xA0;consists of a HER2
monoclonal antibody attached to a topoisomerase I inhibitor
payload, an<font style="font-family: Times New Roman">&#xA0;</font>exatecan derivative,
via a stable tetrapeptide-based cleavable linker.</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic">
Enhertu</font>&#xA0;(5.4mg/kg) is approved in more than 35
countries for the treatment of adult patients with unresectable or
metastatic HER2-positive breast cancer who have received a (or one
or more) prior anti-HER2-based regimen either in the metastatic
setting, or in the neoadjuvant or adjuvant setting and have
developed disease recurrence during or within six months of
completing therapy based on the results from the DESTINY-Breast03
trial.</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic">
Enhertu</font>&#xA0;(5.4mg/kg) is approved in several countries for
the treatment of adult patients with unresectable or metastatic
HER2-positive breast cancer who have received two or more prior
anti-HER2-based regimens based on the results from the
DESTINY-Breast01 trial.</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic">
Enhertu</font>&#xA0;(5.4mg/kg) is approved in Brazil and the US for
the treatment of adult patients with unresectable or metastatic
HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a
prior chemotherapy in the metastatic setting or developed disease
recurrence during or within six months of completing adjuvant
chemotherapy based on the results from the DESTINY-Breast04
trial.</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; font-size: 13px">
Enhertu</font><font style="font-family: Times New Roman">&#xA0;</font><font style="font-size: 13px">(5.4mg/kg) is approved under accelerated approval
in the US for the treatment of adult patients with unresectable or
metastatic non-small cell lung cancer whose tumours have activating
HER2 (ERBB2) mutations, as detected by an FDA-approved test, and
who have received a prior systemic therapy, based on the results of
the DESTINY-Lung02 trial. Continued approval for this indication
may be contingent upon verification and description of clinical
benefit in a confirmatory trial.</font></font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic">
Enhertu</font>&#xA0;(6.4mg/kg) is approved in several countries for
the treatment of adult patients with locally advanced or metastatic
HER2-positive gastric or GEJ who have received a prior
trastuzumab-based regimen based on the results from the
DESTINY-Gastric01 trial.</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-weight: bold; font-style: italic">
Enhertu</font>&#xA0;<font style="font-weight: bold">development
programme</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">A
comprehensive development programme is underway globally,
evaluating the efficacy and safety of&#xA0;<font style="font-style: italic">Enhertu&#xA0;</font>monotherapy across
multiple HER2-targetable cancers, including breast, gastric, lung
and colorectal cancers. Trials in combination with other anticancer
treatments, such as immunotherapy, are also underway.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Regulatory
applications for&#xA0;<font style="font-style: italic">Enhertu</font>&#xA0;in breast and gastric
cancer are currently under review in several other countries based
on the DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04,
DESTINY-Gastric01 and DESTINY-Gastric02 trials,
respectively.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
Daiichi Sankyo collaboration</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Daiichi
Sankyo Company, Limited&#xA0;(TSE: 4568)&#xA0;[referred to as
Daiichi Sankyo] and AstraZeneca entered into a global collaboration
to jointly develop and commercialise&#xA0;<font style="font-style: italic">Enhertu</font>&#xA0;(a HER2-directed ADC)
in&#xA0;<font style="text-decoration: underline; color: #0000FF">March 2019</font>, and
datopotamab deruxtecan (DS-1062; a TROP2-directed ADC)
in&#xA0;<font style="text-decoration: underline; color: #0000FF">July 2020</font>,
except in Japan where Daiichi Sankyo maintains exclusive rights.
Daiichi Sankyo is responsible for the manufacturing and supply
of&#xA0;<font style="font-style: italic">Enhertu</font>&#xA0;and
datopotamab deruxtecan.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
AstraZeneca in gastrointestinal cancers</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">AstraZeneca
has a broad development programme for the treatment of
gastrointestinal (GI) cancers across several medicines and a
variety of tumour types and stages of disease. In 2020, GI cancers
collectively represented approximately 5.1 million new cancer cases
leading to approximately 3.6 million deaths.<font style="font-size: 70%; vertical-align: top">13</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Within
this programme, the Company is committed to improving outcomes in
gastric, liver, biliary tract, oesophageal, pancreatic and
colorectal cancers.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic">
Enhertu</font>, a HER2-directed antibody drug conjugate, is
approved in the US and several other countries for HER2-positive
advanced gastric cancer and is being assessed in colorectal
cancer.&#xA0;<font style="font-style: italic">Enhertu</font>&#xA0;is jointly developed and
commercialised by AstraZeneca and Daiichi Sankyo.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic">
Imfinzi</font>&#xA0;(durvalumab) is approved in the US and several
other countries in combination with chemotherapy (gemcitabine plus
cisplatin) for advanced biliary tract cancer and in the US in
combination with&#xA0;<font style="font-style: italic">Imjudo</font>&#xA0;(tremelimumab) in
unresectable hepatocellular carcinoma.&#xA0;<font style="font-style: italic">Imfinzi</font>&#xA0;is being assessed in
combinations, including with&#xA0;<font style="font-style: italic">Imjudo</font>, in liver, oesophageal and
gastric cancers in an extensive development programme spanning
early to late-stage disease across settings.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic">
Lynparza</font>&#xA0;(olaparib), a first-in-class PARP inhibitor,
is approved&#xA0;in the US and several other countries&#xA0;for the
treatment of BRCA-mutated metastatic pancreatic
cancer.&#xA0;<font style="font-style: italic">Lynparza</font>&#xA0;is developed and
commercialised in collaboration with MSD (Merck &amp; Co., Inc.
inside the US and Canada).</font></div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
AstraZeneca in oncology</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">AstraZeneca
is leading a revolution in oncology with the ambition to provide
cures for cancer in every form, following the science to understand
cancer and all its complexities to discover, develop and deliver
life-changing medicines to patients.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">The
Company's focus is on some of the most challenging cancers. It is
through persistent innovation that AstraZeneca has built one of the
most diverse portfolios and pipelines in the industry, with the
potential to catalyse changes in the practice of medicine and
transform the patient experience.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">AstraZeneca
has the vision to redefine cancer care and, one day, eliminate
cancer as a cause of death.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
AstraZeneca</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">AstraZeneca
(LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and
commercialisation of prescription medicines in Oncology, Rare
Diseases, and BioPharmaceuticals, including Cardiovascular, Renal
&amp; Metabolism, and Respiratory &amp; Immunology. Based in
Cambridge, UK, AstraZeneca operates in over 100 countries and its
innovative medicines are used by millions of patients worldwide.
Please visit&#xA0;<font style="text-decoration: underline; color: #0000FF">astrazeneca.com</font>&#xA0;and
follow the Company on Twitter&#xA0;<font style="text-decoration: underline; color: #0000FF">@</font><font style="text-decoration: underline; color: #0000FF">AstraZeneca</font>.</font></div>
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Contacts</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">For
details on how to contact the Investor Relations Team, please
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contacts, click&#xA0;<font style="text-decoration: underline; color: #0000FF">here</font>.</font></div>
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References</font></div>
<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; font-size: 13px">1.&#xA0;&#xA0; Updated analysis
of DESTINY-Gastric02. Available at:</font><font style="font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://oncologypro.esmo.org/meeting-resources/esmo-congress/updated-analysis-of-destiny-gastric02-a-phase-ii-single-arm-trial-of-trastuzumab-deruxtecan-t-dxd-in-western-patients-pts-with-her2-positive</font><font style="color: #000000; font-size: 13px">.
Accessed November 2022.</font></font></div>
<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-size: 13px">2.&#xA0;&#xA0;</font><font style="font-family: Times New Roman">&#xA0;</font><font style="font-size: 13px">Shitara K, et al. Trastuzumab Deruxtecan in
Previously Treated HER2-Positive Gastric
Cancer.&#xA0;</font><font style="font-style: italic; font-size: 13px">N</font><font style="font-family: Times New Roman">&#xA0;</font><font style="font-style: italic; font-size: 13px">Engl J Med</font><font style="font-family: Times New Roman">&#xA0;</font><font style="font-size: 13px">2020; 382:2419-2430.</font></font></div>
<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 13px">3.&#xA0;&#xA0;
C<font style="background-color: #FFFFFF">asamayor M, et al.
Targeted literature review of the global burden of gastric
cancer.&#xA0;</font><font style="font-style: italic; background-color: #FFFFFF">Ecancermedicalscience</font><font style="background-color: #FFFFFF">.
2018; 12:883;12:883.</font></font></div>
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<font style="font-family: Times New Roman; font-size: 13px"><font style="font-size: 13px">4.&#xA0;&#xA0;</font><font style="font-family: Times New Roman">&#xA0;</font><font style="font-size: 13px">SEER Cancer Stat Facts: Stomach Cancer. Available
at:</font><font style="font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://seer.cancer.gov/statfacts/html/stomach.html</font><font style="font-size: 13px">.
Accessed November 2022.</font></font></div>
<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 13px">5.&#xA0;&#xA0;&#xA0;<font style="background-color: #FFFFFF">Sung.
H et al. Global cancer statistics 2020: GLOBOCAN estimates of
incidence and mortality worldwide for 36 cancers in 185
countries.&#xA0;</font><font style="font-style: italic; background-color: #FFFFFF">CA Cancer J
Clin</font><font style="background-color: #FFFFFF">. 2021;
10.3322/caac.21660.</font></font></div>
<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-size: 13px">6.&#xA0;&#xA0; WHO.&#xA0;</font><font style="font-size: 13px; background-color: #FFFFFF">International Agency
of Cancer Research. Cancer Today. Stomach Incidence. 2020.
Available at:</font><font style="font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px; background-color: #FFFFFF">https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf</font><font style="font-size: 13px; background-color: #FFFFFF">.
Accessed November 2022.</font></font></div>
<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-size: 13px">7.&#xA0;&#xA0; Cancer Research UK.&#xA0;Stomach
Cancer Survival Statistics. Available at:</font><font style="font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/stomach-cancer/survival#heading-Zero</font><font style="font-size: 13px">.
Accessed November 2022.</font></font></div>
<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 13px">8.&#xA0;&#xA0;
Iqbal N, et al.&#xA0;Human Epidermal Growth Factor Receptor 2
(HER2) in Cancers: Overexpression and Therapeutic
Implications.&#xA0;<font style="font-style: italic">Mol Biol
Int</font>. 2014; 2014:852748.</font></div>
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<font style="font-family: Times New Roman; font-size: 13px"><font style="font-size: 13px">9.&#xA0;&#xA0;</font><font style="font-family: Times New Roman">&#xA0;</font><font style="font-size: 13px">Abrahao-Machado LF, et al.&#xA0;HER2 testing in
gastric cancer: An update.&#xA0;</font><font style="font-style: italic; font-size: 13px">World J
Gastroenterol.</font><font style="font-size: 13px">&#xA0;2016;
22(19):4619-4625.</font></font></div>
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<font style="font-family: Times New Roman; font-size: 13px">10.&#xA0;&#xA0;<font style="background-color: #FFFFFF">Orditura
M, et al. "Treatment of gastric cancer."&#xA0;</font><font style="font-style: italic; background-color: #FFFFFF">World Journal of
Gastroenterology</font><font style="background-color: #FFFFFF">:
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<font style="font-family: Times New Roman; font-size: 13px"><font style="font-size: 13px">11.&#xA0;</font><font style="font-family: Times New Roman">&#xA0;</font><font style="font-size: 13px">Thuss-Patience PC, et al.&#xA0;Trastuzumab
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Oncol</font><font style="font-size: 13px">. 2017;
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<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 13px">12.&#xA0; Satoh T,
et al. Lapatinib Plus Paclitaxel Versus Paclitaxel Alone in the
Second-Line Treatment of HER2-Amplified Advanced Gastric Cancer in
Asian Populations: TyTAN-A Randomized, Phase III
Study.&#xA0;<font style="font-style: italic">J Clin
Oncol</font>.2014; 32(19):2039<font style="font-family: Times New Roman">&#x2010;</font>2049.</font></div>
<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 13px">13.&#xA0; WHO.
World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed November 2022.</font></div>
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<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
Adrian Kemp</font></div>
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<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
Company Secretary</font></div>
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<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
AstraZeneca PLC</font></div>
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SIGNATURES</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">Pursuant
to the requirements of the Securities Exchange Act of 1934, the
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by the undersigned, thereunto duly authorized.</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">AstraZeneca
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<font style="font-family: Times New Roman; font-size: 13px">Date:
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<font style="font-family: Times New Roman; font-size: 13px">By: /s/
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<font style="font-family: Times New Roman; font-size: 13px">Name:
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<font style="font-family: Times New Roman; font-size: 13px">Title:
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